No abstract available.
Animals ; Mice* ; Pancreas, Exocrine*

Diabetes can develop as a direct consequence of diseases of the exocrine pancreas. Diabetes due to diseases of the exocrine pancreas is described as pancreatogenic diabetes or type 3c diabetes. Pancreatogenic diabetes is not commonly recognized by clinicians and is frequently misclassified as type 1 diabetes or, more commonly, type 2 diabetes. The prevalence and clinical importance of pancreatogenic diabetes have been underestimated and underappreciated. Pancreatogenic diabetes has a unique pattern of hormonal and metabolic characteristics. The failure to correctly diagnose pancreatogenic diabetes leads to failure to implement an appropriate medical therapy in these patients. We will review the clinical implications and relevance of pancreatogenic diabetes.
Diabetes Mellitus ; Humans ; Pancreas ; Pancreas, Exocrine ; Prevalence

BACKGROUND AND OBJECTIVES: Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder resulting out of T cell mediated destruction of pancreatic beta cells. Immunomodulatory properties of mesenchymal stem cells may help to regenerate beta cells and/or prevent further destruction of remnant, unaffected beta cells in diabetes. We have assessed the ability of umbilical cord derived MSCs (UCMSCs) to differentiate into functional islet cells in vitro. METHODS AND RESULTS: We have isolated UCMSCs and allowed sequential exposure of various inducing agents and growth factors. We characterized these cells for confirmation of the presence of islet cell markers and their functionality. The spindle shaped undifferentiated UCMSCs, change their morphology to become triangular in shape. These cells then come together to form the islet like structures which then grow in size and mature over time. These cells express pancreatic and duodenal homeobox -1 (PDX-1), neurogenin 3 (Ngn-3), glucose transporter 2 (Glut 2) and other pancreatic cell markers like glucagon, somatostatin and pancreatic polypeptide and lose expression of MSC markers like CD73 and CD105. They were functionally active as demonstrated by release of physiological insulin and C-peptide in response to elevated glucose concentrations. CONCLUSIONS: Pancreatic islet like cells with desired functionality can thus be obtained in reasonable numbers from undifferentiated UCMSCs in vitro. This could help in establishing a "very definitive source" of islet like cells for cell therapy. UCMSCs could thus be a game changer in treatment of diabetes.
C-Peptide ; Cell- and Tissue-Based Therapy* ; Diabetes Mellitus, Type 1 ; Genes, Homeobox ; Glucagon ; Glucose ; Glucose Transport Proteins, Facilitative ; Insulin* ; Insulin-Secreting Cells ; Intercellular Signaling Peptides and Proteins ; Islets of Langerhans ; Mesenchymal Stromal Cells* ; Pancreatic Polypeptide ; Somatostatin ; Stem Cells ; Umbilical Cord*

The orifice of duodenal papilla is only about 1 mm in diameter. As much as 2,000 ml of bile and pancreatic juice pass through its sphincter zone into the duodenum each day. Since the sphincter of Oddi regulates the flow of bile and pancreatic juice, a disorder of the sphincter can disturb the smooth outflow of bile and pancreatic juice and produce secondary abnormalities in the biliary tract or the exocrine pancreas. (continue...)
Bile ; Biliary Tract ; Duodenum ; Humans ; Manometry* ; Pancreas, Exocrine ; Pancreatic Ducts* ; Pancreatic Juice ; Pancreatitis, Chronic* ; Sphincter of Oddi

The orifice of duodenal papilla is only about 1 mm in diameter. As much as 2,000 ml of bile and pancreatic juice pass through its sphincter zone into the duodenum each day. Since the sphincter of Oddi regulates the flow of bile and pancreatic juice, a disorder of the sphincter can disturb the smooth outflow of bile and pancreatic juice and produce secondary abnormalities in the biliary tract or the exocrine pancreas. (continue...)
Bile ; Biliary Tract ; Duodenum ; Humans ; Manometry* ; Pancreas, Exocrine ; Pancreatic Ducts* ; Pancreatic Juice ; Pancreatitis, Chronic* ; Sphincter of Oddi

No abstract available.
Islets of Langerhans* ; Pancreas*

There are numerous studies on transepithelial transports in duct cells including Cl and/or HCO3. However, studies on transepithelial K transport of normal duct cells in exocrine glands are scarce. In the present study, we examined the characteristics of K currents in single duct cells isolated from guinea pig pancreas, using a whole-cell patch clamp technique. Both Cl and K conductance were found with KCl rich pipette solutions. When the bath solution was changed to low Cl, reversal potentials shifted to the negative side, 75 4 mV, suggesting that this current is dominantly selective to K. We then characterized this outward rectifying K current and examined its Ca2 dependency. The K currents were activated by intracellular Ca2. 100 nM or 500 nM Ca2 in pipette significantly (P< 0.05) increased outward currents (currents were normalized, 76.8 7.9 pA, n=4 or 107.9 35.5 pA, n=6) at 100 mV membrane potential, compared to those with 0 nM Ca2 in pipette (27.8 3.7 pA, n=6). We next examined whether this K current, recorded with 100 nM Ca2 in pipette, was inhibited by various inhibitors, including Ba2, TEA and iberiotoxin. The currents were inhibited by 40.4 % (n=3), 87.0 % (n=5) and 82.5 % (n=9) by 1 mM Ba2, 5 mM TEA and 100 nM iberiotoxin, respectively. Particularly, an almost complete inhibition of the current by 100 nM iberiotoxin further confirmed that this current was activated by intracellular Ca2. The K current may play a role in secretory process, since recycling of K is critical for the initiation and sustaining of Cl or HCO3 secretion in these cells.
Animals ; Baths ; Exocrine Glands ; Guinea Pigs ; Membrane Potentials ; Pancreas ; Pancreatic Ducts* ; Recycling ; Secretory Pathway ; Tea

Insulin is produced and secreted by pancreatic β cells in the pancreas, which plays a key role in maintaining euglycemia. Insufficient secretion or deficient usage of insulin is the main cause of diabetes mellitus (DM). Drug therapy and islets transplantation are classical treatments for DM. Pancreatic β cell replacement therapy could help patients to get rid of drugs and alleviate the problem of lacking in transplantable donors. Pancreatic β-like cells can be acquired by cell reprogramming techniques or directed induction of stem cell differentiation. These cells are proved to be functional both in vitro and in vivo. Some hospitals have already performed clinical trials for pancreatic β cell replacement therapy. Functional pancreatic β-like cells, which obtained from in vitro pathway, could be a reliable source of cell therapy for treating DM. In this review, the approaches of obtaining pancreatic β cells are summarized and the remaining problems are discussed. Some thoughts are provided for further acquisition and application of pancreatic β cells.
Cell Differentiation ; Diabetes Mellitus/therapy* ; Humans ; Insulin/metabolism* ; Insulin-Secreting Cells/metabolism* ; Islets of Langerhans Transplantation ; Pancreas/metabolism*

A putative polypeptide hormone identified as amylin[islet amyloid polypeptide] is synthesized and co-localized with insulin in B cells of pancreatic islets in several animal species including man. However, there is growing evidence that somatostatin cells are also expressed and contained amylin in the pancreatic islets of the rat The aim of the present study was to investigate the immunocytochemical expression of the amylin within the endocrine pancreas of the man, rabbit and guinea pig, with special reference to the possible ability of islet cells other than insulin cells to synthesize amylin. For this purpose serial sections of the pancreatic islets were stainedimmunocytochemically using anti-amylin, anti-insulin, anti-glucagon, anti-somatostatin antisera. In serial sections of pancreatic islets of the man and rabbit, it was shown that amylin immunoreactivity occurred in insulin-reactive B cells predominantly located in interior of the islets. In contrast, amylin immunoreacivity appeared in glucagon-reactive A cells peripherally located in the islets of the guinea pig. These results suggest that in both the man and rabbit, amylin is synthesized by B cells for subsequent co-secretion with insulin, and that in guinea pig, amylin is synthesized by A cells for co-secretion with glucagon. It thus appears that amylin release may be mediated by different secretory mechanisms according to animal species.
Amyloid ; Animals ; B-Lymphocytes ; Glucagon ; Guinea Pigs* ; Guinea* ; Immune Sera ; Immunohistochemistry ; Insulin ; Islet Amyloid Polypeptide* ; Islets of Langerhans* ; Rats ; Somatostatin-Secreting Cells

Diabetes Mellitus is a metabolic disease caused by impaired insulin secretion of pancreatic beta cells and increased insulin resistance of peripheral tissues. In Asian T2DM, progressive loss of beta cells mass and concomitant reduction of insulin secretion are more fundamental problems than peripheral insulin resistance. To solve this problem, research fields about investigation how stimulated islet cell growth and block the islet cell death is getting more important. Recently introduced drug, Glucagon like peptide-1 (GLP-1) has many beneficial roles in treatment of diabetes. GLP-1 stimulated glucose dependent insulin secretion and also can preserve beta cell mass through stimulation of beta cell growth and differentiation and protection of beta cell death from hyperglycemic stress. After treatment of GLP-1 or Exendin-4 (GLP-1 receptor agonist), beta cell mass is increased in animal models. This can be achieved through beta cell proliferation in islet or differentiation from intrapancreatic progenitor cells like ductal epithelium. The mechanism of beta cell proliferation is mediated by the PKA-CREB pathway. After activation of GLP-1 receptor, intracellular cAMP is elevated and then it activates PKA and CREB phosphorylation. Translocation of CREB into the nucleus up-regulates PDX-1 andIRS-2. Another pathway for beta cell proliferation is trans-activation of EGFR via c-Src after GLP-1 receptor activated. The notch pathway, major determinant of pancreas development in the embryonic stage, can be participate beta mass preservation through activation of gamma secretase in the beta cell membrane. Cleaved intracellular part of the notch translocates to the nucleus and binds to the pdx-1 promoter region. In hyperglycemia, oxidative and endoplasmic reticulum (ER) stress can be caused by apoptosis of the beta cell. Protection of apoptosis is another tool for beta cell mass preservation. After treatment of GLP-1 or exendin-4, beta cell apoptosis induced by oxidative and ER stress can be protected. GLP-1 can modulate JNK and GSK 3beta activation and ER chaperone and ER stress response. In treatment of diabetes, GLP-1 increases insulin secretion with glucose dependent manner and also preserves beta cell mass against progressive beta cell loss
Amyloid Precursor Protein Secretases ; Apoptosis ; Asian Continental Ancestry Group ; Cell Death ; Cell Membrane ; Cell Proliferation ; Diabetes Mellitus ; Endoplasmic Reticulum ; Epithelium ; Glucagon ; Glucagon-Like Peptide 1 ; Glucose ; Humans ; Hyperglycemia ; Insulin ; Insulin Resistance ; Insulin-Secreting Cells ; Islets of Langerhans ; Metabolic Diseases ; Models, Animal ; Pancreas ; Peptides ; Phosphorylation ; Promoter Regions, Genetic ; Receptors, Glucagon ; Stem Cells ; Venoms ; Glucagon-Like Peptide-1 Receptor